Potassium Carbonate → HCID 86712914, compound

HRID 1424065Notes

Reaction equation

HRID 1424065 reaction equation
[Si]([O:8][CH2:9][C:10]1([CH3:38])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:28]=[CH:27][C:26](B5OC(C)(C)C(C)(C)O5)=[CH:25][CH:24]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1)(C(C)(C)C)(C)C.Cl[C:40]1[CH:45]=[C:44](Cl)[N:43]=[CH:42][N:41]=1.[C:47](=O)([O-])[O-:48].[K+].[K+].C(=O)([O-])O.[Na+]>C(COC)OC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:47][O:48][C:44]1[N:43]=[CH:42][N:41]=[C:40]([C:26]2[CH:25]=[CH:24][C:23]([C:20]3([C:17]4[N:13]5[CH2:14][CH2:15][S:16][C:10]([CH2:9][OH:8])([CH3:38])[CH2:11][C:12]5=[N:19][N:18]=4)[CH2:22][CH2:21]3)=[CH:28][CH:27]=2)[CH:45]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 709434,6-DichloropyrimidineHCID 516892Sodium BicarbonateHCID 867128608-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

Product 1

HCID 86712914HCID 86712914, compoundYield 52%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of the compound (1.39 g, 2.5 mmol) obtained in Example 16-5), 4,6-dichloropyrimidine (1.49 g, 10 mmol), tetrakis(triphenylphosphine)palladium(0) (577 mg, 0.5 mmol), and potassium carbonate (691 mg, 5 mmol) in dimethoxyethane (10 mL) and water (2.5 mL) was stirred at 130° C. for 1.5 h under microwave irradiation. The reaction mixture was cooled to room temperature, saturated aqueous sodium hydrogencarbonate was added to the reaction mixture, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, a solution of 4 M hydrochloric acid (1,4-dioxane solution, 2.5 mL) in methanol (10 mL) was added to the residue, and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate was added to the residue, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient) to obtain the title compound (551 mg, 52%) as a colorless solid.

Workup

  1. extractionthe mixture was extracted with dichloromethane
  2. washthe organic layer was washed with saturated sodium chloride solution
  3. dry with materialdried with anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. additiona solution of 4 M hydrochloric acid (1,4-dioxane solution, 2.5 mL) in methanol (10 mL) was added to the residue
  7. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate
  8. additionwas added to the residue
  9. extractionthe mixture was extracted with dichloromethane
  10. washthe organic layer was washed with saturated sodium chloride solution
  11. dry with materialdried with anhydrous sodium sulfate
  12. filtrationAfter filtration
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customthe residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient)

Sources & evidence

ORD record
ord-166f4755e58b4679aa1b4c3a11dd60bb
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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